Calcium phosphate based cements (CaPC) have been used as bone substitutes and bone grafts for nearly twenty years. In the 1980s, the research was focused on developing a formulation that was biocompatible for the intended use of clinical applications. These CaPC formulations have historically been provided in the form of a powder and liquid system, which upon mixing becomes a paste and goes through a partial dissolution that initiates a precipitation reaction resulting in the setting of the cement. Often such cements are based on an acid-base reaction to form a salt which usually takes the form of the calcium phosphate phase identified as hydroxyapatite or brushite.
Most of the presently available calcium phosphate precursor cement formulations are still a powder/liquid system wherein the powder and the liquid components are separately packaged and only to be combined prior to use at time of surgery. The mixing is accomplished by either (a) manual mixing, or (b) use of a mechanical based mixing system provided in a commercial product. However, both approaches have some shortcomings. The manual system is sometimes perceived to be time consuming, and user dependent/sensitive. The custom designed mechanical systems aim to provide a more satisfactory user experience by providing consistency and reproducibility for the end user, but are still considered to be cumbersome, difficult to use and cost ineffective.
Accordingly, there have been studies reported with the aim to develop premixed, self-hardening, cement pastes. For example, U.S. Pat. No. 6,793,725 describes a self-hardening calcium phosphate based bone cement paste that is mixed with liquid glycerol, hydroxypropyl methylcellulose and sodium phosphate. This premixed paste formulation allegedly remains stable over a period of time and hardens only when delivered to a desired site in a human body. This premixed paste formulation, however, does not exhibit a good washout resistance when it is applied to an open wet field in a human body, and is therefore limited in utility.
U.S. Patent Publication No. 2006/0263443 also discloses a premixed self-hardening calcium phosphate based bone cement paste containing a gelling agent, such as hydroxymethyl cellulose, carboxymethyl cellulose, chitosan, collagen, gum, gelatin and alginate, to enhance paste cohesiveness and washout resistance. This type of cement, allegedly possesses excellent physical properties, but it is also limited in utility since cement hardening in the interior of the cement mass is slow under some clinical bone grafting conditions, for instance, wherein the amount of water available from the tissue is limited, or wherein the interior of the cement is more than several millimeters away from the nearest graft-tissue interface.
U.S. Patent Publication No. 2007/0092580 teaches a self-setting dual phase cement precursor system composed of a first and second discrete containers, at least one of which is aqueous. The cement formed by combining these two phases, however, do not have a long-term shelf life, as the phases in each of these two pastes packaged in separate containers tend to destabilize/separate during storage. This is especially true after the dual paste system is sterilized using gamma radiation. Therefore, this formulation also is limited in utility.
The present invention aims at responding to the currently unanswered user need for providing a premixed dual paste injectable bone cement precursor system that is shelf stable even after it is sterilized using gamma radiation for in vivo usage, and that rapidly sets as a biocompatible bone cement possessing excellent physical properties when combined.